Dual targeting ligand for cancer diagnosis and treatment

Abstract

Disclosed are compositions and methods relating to prostate cancer. In particular, disclosed are bivalent targeting ligands that specifically bind prostate specific membrane antigen and gastrin-releasing peptide receptor. Bivalent binding agents disclosed herein can be used to image a tissue in a subject in need thereof and to diagnose prostate cancer in a subject in need thereof. Bivalent binding agents disclosed herein can be used to treat prostate cancer in a subject in need thereof.

What is claimed is: 
     
       1. A bivalent binding agent of formula (I)
   [DUPA-6-Ahx-Lys(DOTA)-X-RM2]  (I)
 
 wherein X is selected from the group consisting of 5-aminovaleric acid (5-Ava), 6-amino hexanoic acid (6-Ahx), 8-aminooctanoic acid) (8Aoc), and paraamino benzoic acid (AMBA). 
 
     
     
       2. A bivalent binding agent of formula (II)
   [DUPA-6-Ahx-Lys(M-DOTA)-X-RM2]  (II)
 
 wherein X is selected from 5-aminovaleric acid (5-Ava), 6-amino hexanoic acid (6-Ahx), 8-aminooctanoic acid) (8Aoc), and paraamino benzoic acid (AMBA); and wherein M is selected from Gallium (Ga), Indium (In), Lutetium (Lu), Yttrium (Y), Samarium (Sm), Promethium (Pm),  67 Ga,  68 Ga,  111 In,  177 Lu,  90 Y,  86 Y,  153 Sm, and  149 Pm. 
 
     
     
       3. A method of imaging a tissue in a subject in need thereof having or suspected of having prostate cancer, the method comprising:
 administering to the subject having or suspected of having prostate cancer a bivalent binding agent of formula (II)
   [DUPA-6-Ahx-Lys(M-DOTA)-X-RM2]  (II)
 
 
 
       wherein X is selected from 5-aminovaleric acid (5-Ava), 6-amino hexanoic acid (6-Ahx), 8-aminooctanoic acid) (8Aoc), and paraamino benzoic acid (AMBA); and wherein M is selected from  67 Ga,  68 Ga,  111 In,  86 Y, and  177 Lu; and
 applying an imaging technique to detect emitted gamma rays. 
 
     
     
       4. The method of  claim 3 , wherein the imaging technique is selected from the group consisting of positron-emission tomography (PET) and single photon emission computed tomography (SPECT). 
     
     
       5. A method of diagnosing prostate cancer in a subject having or suspected of having prostate cancer, the method comprising:
 administering to the subject a bivalent binding agent of formula (II)
   [DUPA-6-Ahx-Lys(M-DOTA)-X-RM2]  (II)
 
 
 
       wherein X is selected from 5-aminovaleric acid (5-Ava), 6-amino hexanoic acid (6-Ahx), 8-aminooctanoic acid) (8Aoc), and paraamino benzoic acid (AMBA); and wherein M is selected from  67 Ga,  68 Ga,  111 In,  86 Y, and  177 Lu; applying an imaging technique to detect emitted gamma rays; and diagnosing the subject as having prostate cancer based on uptake of the bivalent binding agent as detected in the imaging of the subject. 
     
     
       6. The method of  claim 5 , wherein the imaging technique is selected from the group consisting of positron-emission tomography (PET) and single photon emission computed tomography (SPECT). 
     
     
       7. A method of treating prostate cancer in a subject having or suspected of having prostate cancer, the method comprising:
 administering to the subject a bivalent binding agent of formula (II)
   [DUPA-6-Ahx-Lys(M-DOTA)-X-RM2]  (II)
 
 
 
       wherein X is selected from 5-aminovaleric acid (5-Ava), 6-amino hexanoic acid (6-Ahx), 8-aminooctanoic acid) (8Aoc), and paraamino benzoic acid (AMBA); and wherein M is selected from  177 Lu,  90 Y,  153 Sm, and  149 Pm. 
     
     
       8. The method of  claim 7 , wherein the subject is administered about 100 μg/70 kg of the bivalent binding agent of formula (II). 
     
     
       9. The method of  claim 7 , wherein the subject is administered less than 100 μg/70 kg of the bivalent binding agent of formula (II).